Phenobarbital is a barbiturate that reduces excitatory synaptic responses by acting on GABAA receptors. It is most commonly used in the treatment of seizures, including tonic-clonic seizures and in status epilepticus. Studies have also shown its efficacy in treating benzodiazepine toxification and perinatal asphyxia. [1, 2]
The therapeutic reference range of phenobarbital varies by age, as follows:
Infants and children (< 5 years): 15-30 µg/mL
Adults: 15-40 µg/mL
The minimum toxic level is 30 µg/mL.
The toxic concentration/critical laboratory value is 60 µg/mL or more.
The normal terminal elimination half-life also varies by age, as follows:
Infants and children (< 5 years): 40-70 hours
Adults: 50-140 hours
Phenobarbital’s usual duration of effect exceeds 6-12 hours.
The volume of distribution is 0.5-1 L/kg.
The phenobarbital level is used to measure the concentration of the drug in a patient’s blood.
The phenobarbital level can be correlated with a patient’s clinical presentation to ascertain the therapeutic phenobarbital level. Of note, other medications, including antihistamines, corticosteroids, oral contraceptives, and other antiepileptics, may alter the serum level of phenobarbital; therefore, it is important to closely monitor patients receiving these medications to closely monitor phenobarbital levels.
Phenobarbital levels must be monitored for the entire administration duration.
Collection and Panels
Specimen: Whole blood/serum/plasma
Container: Red-top tube (plain, no gel)
Collection method: Routine venipuncture
Draw volume: 1 mL; 0.4 mL is the minimum
Phenobarbital is a barbiturate that reduces excitatory synaptic responses by acting on GABAA receptors. It is most commonly used in the treatment of seizures, including tonic-clonic seizures and in status epilepticus. Phenobarbital is usually a second- or third-line agent for these indications (after diazepam or phenytoin), as the onset of drug effects are delayed. The onset of effect after intravenous phenobarbital administration is within 5 minutes, and peak effects occur within 30 minutes. The only possible exception to this rule is in the case of drug-induced seizures, particularly with seizures secondary to theophylline ingestion, in which phenobarbital may be administered prior to phenytoin.
Symptoms of phenobarbital toxicity include sedation, ataxia, nystagmus, hyperactivity and irritability (in pediatric patients), and confusion and agitation (in elderly populations). Moreover, sedation can be seen in all patients upon initiation of therapy, but tolerance to this symptom occurs with chronic dosing. Phenobarbital, when combined with other sedative medications, has additive effects on both CNS and respiratory depression.
There is no exact relationship between the concentration of phenobarbital in the plasma and its therapeutic effects, however, plasma levels of 10-35 µg/mL are recommended for seizure management. Steady state is usually attained between 2-3 weeks after initiation of drug therapy.
Phenobarbital is metabolized principally in liver by microsomal enzymes, with up to 25% of the phenobarbital dose eliminated by pH-dependent renal excretion. The drug is contraindicated in patients with hepatic dysfunction (as it can increase the half-life) and porphyria. With long-term use, phenobarbital can induce hepatic CYP enzymes—principally CYP2C9. Phenobarbital is 40%-60% bound to plasma proteins and body tissues.
The half-life of phenobarbital increases during pregnancy in part because of volume expansion.
Recent studies on phenobarbital level monitoring have examined the effects of age on phenobarbital clearance. A study by Messina et al in 2005 demonstrated that, with age, the rate of phenobarbital clearance decreases. This can be most likely attributed to decreased hepatic drug clearing and decrease in glomerular filtration rate found in the elderly population. As a result, older patients may require a lower dose of phenobarbital to achieve comparable therapeutic effects than younger patients.